Recombinant human antibodies for therapy and prevention of polyomavirus-related diseases

Abstract

Provided are novel human-derived antibodies specifically recognizing polyomavirus polypeptides, preferably capable of binding to polyomaviruses of the type of JC virus (JCV) and / or BK virus (BKV) as well as methods related thereto. Furthermore, assays and kits related to antibodies specific for polyomaviruses, polyomavirus VP1 and or polyomavirus VP1 Virus-Like Particles (VLPs), preferably of the type of JCV and / or BKV, are disclosed. The human-derived antibodies as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for polyomavirus targeted immunotherapy and diagnostics.

Description

RELATED APPLICATIONS[0001]This application is a division of U.S. application Ser. No. 15 / 678,965 (now patented as U.S. Pat. No. 10,450,365), which is a continuation of U.S. application Ser. No. 14 / 758,615 (now patented as U.S. Pat. No. 9,771,413), which is a U.S. National Phase under 35 U.S.C. § 371 of International Application No. PCT / EP2014 / 050024, filed on Jan. 2, 2014, which claims priority to EP 12199837.1, filed on Dec. 31, 2012 and U.S. 61 / 747,541, filed on Dec. 31, 2012, the contents of each of which are hereby incorporated by reference in their entirety for all purposes.SEQUENCE LISTING[0002]This application contains a Sequence Listing which has been submitted electronically in ASCII format via EFS-Web and is incorporated by reference in its entirety. Said ASCII copy is named SL.txt, is 265 kilobytes in size, and was created on Sep. 11, 2019.FIELD OF THE INVENTION[0003]The present invention generally relates to novel molecules specifically binding to human polyomavirus and / ...

AI Technical Summary

Benefits of technology

The therapeutic approach of this patent lies in the use of antibodies derived from healthy elderly human subjects who have recovered from PML and PML-IRIS, a disease related to polyomavirus. These antibodies can prevent or reduce the risk of developing a clinical disease by targeting the polyomavirus, its VP1 molecule, and / or its VLP form. The antibodies have also undergone somatic maturation, improving their effectiveness and selectivity in binding to the target molecule.

Problems solved by technology

PML is an opportunistic and often fatal infection that occurs in states of immunocompromise such as human immunodeficiency virus (HIV) infection, cancer, organ transplantation, haematological malignancies or rarely during autoimmune diseases.

Furthermore, immunomodulatory therapies that target immune cells or therapies for conditions such as Multiples Sclerosis (MS) as well as patients with liver or renal impairment, and patients with psoriasis, systemic lupus erythematosus, chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma, and Crohn's disease have an increased risk of incident of PML.

Similarly, recent estimates assume an incidence of PML in 1:500 MS patients, who are treated with natalizumab, with a strong increase beyond 2 years of treatment thus jeopardizing the further use of this currently most effective treatment for MS.

However, immune-compromised patients cannot repress anymore the viral replication and BKV reactivation can lead to several diseases.

BKV became mainly an issue in cases of severe immune depression, for example in patients who received a transplant and who therefore had to take immunosuppressive drugs.

In those patients, the virus can multiply inside the graft cells and cause a disease named BK nephropathy which can finally lead to graft loss.

BKV is also an issue for patients who received a bone marrow transplant and who can develop a hemorrhagic cystitis.

There is no available treatment to clear BKV infection.

Some small molecules have been reported to limit the viral spread but their mechanisms of action are not entirely understood.

However, this could also lead to graft rejection.

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